Does Improving HbA1c Also Improve Depressive Symptoms?
Andreas Schmitt, Magdalena Beran, Anouk Geraets, Marjolein M. Iversen, Giesje Nefs, Arie Nouwen, Frans Pouwer, Jörg W. Huber, Miranda T. Schram
Associations between HbA1c Reduction and Change in Depressive Symptoms following Glucose-lowering Treatment in Adults: A Systematic Review of Intervention Studies. Curr Diabetes Rev . 16 Aug 2023;20(3):e020623217607.
Depression and diabetes are closely linked, and hyperglycaemia has been proposed as a key mechanism connecting the two conditions. In earlier work, this research group demonstrated a bidirectional longitudinal association between depressive symptoms and HbA1c levels, showing that higher depressive symptoms predict higher HbA1c over time and that higher HbA1c increases the risk of subsequent depression. Although these associations were statistically significant, effect sizes were small and causality could not be established.
An important next question is whether actively lowering HbA1c through treatment leads to meaningful improvements in depressive symptoms. Randomized controlled trials of glucose-lowering interventions provide an opportunity to examine this temporal relationship more directly. This systematic review therefore shifts the focus from observational associations to treatment-related changes in HbA1c and depressive symptoms.
The authors conducted a systematic review of randomized controlled trials published between 2000 and 2020 that evaluated glucose-lowering interventions and included assessments of depressive symptoms. Multiple databases were searched, study quality was assessed using the Cochrane Risk of Bias tool, and the review was registered in PROSPERO. The primary aim was to evaluate whether reductions in HbA1c following treatment were associated with changes in depressive symptoms.
Key findings:
- Twelve randomized controlled trials met the inclusion criteria, out of more than 1,600 screened studies.
- Most included studies had a high risk of bias, limiting confidence in causal inference.
- Baseline depressive symptom levels were generally low, reducing the likelihood of detecting improvement after treatment.
- Five studies reported greater HbA1c reductions in intervention groups, but only three of these also observed greater reductions in depressive symptoms.
- None of the studies that directly analysed the association between HbA1c change and depressive symptom change found a statistically significant relationship.
Together with the authors’ earlier findings of a bidirectional association between depressive symptoms and HbA1c, this review suggests that lowering HbA1c alone does not reliably lead to improvements in depressive symptoms. The results highlight the need for future glucose-lowering trials to include depressive symptoms as an outcome, particularly in populations with elevated baseline distress, to better understand when and how glycaemic and mental health outcomes interact.
Concluding, the authors state
"We found insufficient available data to estimate the association between HbA1c reduction and depressive symptom change following glucose-lowering treatment" -
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